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Updated: Sep 12, 2025
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Adaptor protein complex 1 gamma 1 subunit is an important host factor involved in both Zika virus and dengue virus
Jinna Yang1, Changbai Huang1, Yao Feng1
1Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Guangzhou, 510080, China; Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Abstract:
Mosquito-borne flaviviruses, such as Zika virus (ZIKV) and dengue virus (DENV), cause diverse severe clinical manifestations including fever, rash, hepatitis, arthralgia, and congenital anomalies. Here, we identified a host factor, the adaptor protein complex 1 gamma 1 subunit (AP1G1), which plays an important role in both ZIKV and dengue virus 2 (DENV2) infections. We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference (RNAi) techniques. Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines. Intriguingly, depletion of AP1G1 results in a significant reduction in ZIKV at an early stage, but decreases DENV2 replication levels during the late stage, suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2. Furthermore, we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays. Mechanistically, we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein (E protein). This interaction promotes the fusion of viral and endosomal membranes, during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm, a process that facilitates viral replication. However, for DENV2 infection, AP1G1 primarily affects its viral RNA replication stage, rather than the fusion of virus-endosomal membrane. Taken together, our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms, highlighting its potential as a therapeutic target for antiviral strategies.
Insights
The adaptor protein complex 1 gamma 1 subunit (AP1G1) promotes Zika virus (ZIKV) and dengue virus 2 (DENV2) replication. Depleting AP1G1 hinders viral entry for ZIKV and RNA replication for DENV2, suggesting AP1G1 as an antiviral target.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Mosquito-borne flaviviruses like Zika virus (ZIKV) and dengue virus (DENV) cause significant global health issues, including fever, rash, hepatitis, and congenital anomalies.
- Understanding host-pathogen interactions is crucial for developing effective antiviral therapies against these emerging infectious diseases.
Purpose of the Study:
- To identify and characterize host factors involved in ZIKV and DENV2 replication.
- To elucidate the specific mechanisms by which identified host factors influence viral propagation.
- To evaluate the potential of these host factors as therapeutic targets for flaviviral infections.
Main Methods:
- CRISPR/Cas9 gene editing and RNA interference (RNAi) were employed to deplete the adaptor protein complex 1 gamma 1 subunit (AP1G1).
- Viral replication assays were performed in multiple human cell lines to assess the impact of AP1G1 depletion on ZIKV and DENV2.
- Inhibitor experiments and fluorescence labeling assays were utilized to investigate the role of AP1G1 in viral entry and membrane fusion processes.
Main Results:
- Depletion or knockout of AP1G1 significantly reduced ZIKV and DENV2 replication in human cell lines.
- AP1G1 depletion impaired ZIKV replication at an early stage, specifically by mediating viral-endosomal membrane fusion through interaction with the ZIKV E protein.
- In contrast, AP1G1 depletion affected DENV2 replication during a later stage, primarily impacting viral RNA replication rather than membrane fusion.
Conclusions:
- The adaptor protein complex 1 gamma 1 subunit (AP1G1) acts as a pro-viral factor in both ZIKV and DENV2 infections.
- AP1G1 employs distinct mechanisms to facilitate ZIKV and DENV2 replication, highlighting differential host-pathogen interactions.
- AP1G1 represents a promising therapeutic target for developing novel antiviral strategies against ZIKV and DENV infections.
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